Plasminogen activator inhibitor‐1 (PAI‐1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI‐1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI‐1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the “PAI‐1 paradox”. Many factors are responsible for the upregulation of PAI‐1 in the tumor microenvironment. We hypothesize that there is a breast cancer (...) predisposition to a more aggressive stage when PAI‐1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the “PAI‐1 cycle”. Sustained by MetS, adipocytokines alter PAI‐1 expression to promote angiogenesis, tumor‐cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI‐1 synthesis. All of these factors culminate in a chemotherapy‐resistant breast tumor microenvironment. The PAI‐1 cycle may partly explain the PAI‐1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI‐1 and how an increased level of PAI‐1 can be linked to a poor prognosis. BioEssays 29:1029–1038, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

CYBATHLON is an international championship where people with severe physical disabilities compete with the aid of state-of-the-art assistive technology. In one of the disciplines, the BCI Race, tetraplegic pilots compete in a computer game race by controlling an avatar with a brain-computer interface. This competition offers a perfect opportunity for BCI researchers to study long-term training effects in potential end-users, and to evaluate BCI performance in a realistic environment. In this work, we describe the BCI system designed by the team (...) Mirage91 for participation in the CYBATHLON BCI Series 2019, as well as in the CYBATHLON 2020 Global Edition. Furthermore, we present the BCI’s interface with the game and the main methodological strategies, along with a detailed evaluation of its performance over the course of the training period, which lasted 14 months. The developed system was a 4-class BCI relying on task-specific modulations of brain rhythms. We implemented inter-session transfer learning to reduce calibration time, and to reinforce the stability of the brain patterns. Additionally, in order to compensate for potential intra-session shifts in the features’ distribution, normalization parameters were continuously adapted in an unsupervised fashion. Across the aforementioned 14 months, we recorded 26 game-based training sessions. Between the first eight sessions, and the final eight sessions leading up to the CYBATHLON 2020 Global Edition, the runtimes significantly improved from 255 ± 23 s to 225 ± 22 s, respectively. Moreover, we observed a significant increase in the classifier’s accuracy from 46 to 53%, driven by more distinguishable brain patterns. Compared to conventional single session, non-adaptive BCIs, the inter-session transfer learning and unsupervised intra-session adaptation techniques significantly improved the performance. This long-term study demonstrates that regular training helped the pilot to significantly increase the distance between task-specific patterns, which resulted in an improvement of performance, both with respect to class separability in the calibration data, and with respect to the game. Furthermore, it shows that our methodological approaches were beneficial in transferring the performance across sessions, and most importantly to the CYBATHLON competitions. (shrink)

It is noteworthy that much of recent liberal scholarship aimed at empowering aboriginal peoples, and supporting their land rights, has often unwittingly embraced the conservative Lockean‐Nozickian tradition rather than the tradition of left‐leaning thinkers. Many of the supporters of aboriginal land rights tend to view property rights as contingently determined historical entitlements which are established independently of the state’s authority, thereby creating structures which morally bind the authority of the state. This, in fact, also represents the view of the conservative (...) supporters of untrammelled capitalism. Secondly, there is often little discussion of the bundle of rights which are derived from these acts of original acquisition. This may lead one to the assumption that these supporters of aboriginal land rights agree with the conservative view that all the recognised components of modern liberal ownership, from the right to use, to the right to income, are acquired in the initial events associated with historical entitlement. It is my argument in this paper that basing aboriginal land claims solely on customary historical entitlement results in too close an alignment with a conservative ideology which has been used to support unrestrained capitalism. (shrink)

Apologists for Christianity and Judaism have argued that their religions do not support an exploitative attitude towards the environment. L.H. Steffen, in particular, argues that it is the Hellenic rather than the (Judaeo-Christian tradition which promotes the instrumentalist view of nature. In contrast, I argue that Christianity is and has been an amalgam of the Hellenic and Hebrew traditions. In the course of this paper I indicate certain salient Hellenic influences which were prominent in medieval Christianity. I subsequently point out (...) that, contrary to Steffen's allegations, these influences originally contributed to a non-exploitative attitude to the natural world by the very nature of their anti-materialist prescriptions. However, with the Renaissance and the Reformation, religious attitudes shifted and a new religious morality was generated, one which associated morality and spiritual achievement with intense engagement in the material world and the exploitation of this world in the end of personal prosperity. In part I demonstrate this alteration in perspective by reference to the shifting religious attitudes towards ownership and property. (shrink)

Communitarians have alleged a connection between according specialrights to community groupings and preserving the indigenous cultureand the social cohesion of the original community. This paperconcentrates upon special group rights associated with land tenurenow maintained by Fijian Mataqali and traditional land owninggroups in Papua New Guinea. The first section of the paper assessesand compares the social consequences of each of these systems withspecial attention to the preservation of traditional culture.However, in the case of Fiji, it is undeniable that the mataqaliland tenure (...) system has given indigenous Fijians politicaladvantages over non-indigenous Fijians, most specifically theFijian Indians. Though special land rights can possibly bejustified on the grounds of cultural preservation, their existencedoes raise this further issue of fairness. Moral considerations basedupon the territorial sovereignty of indigenous nations, rather thancommunitarian arguments, may offer a more convincing justificationof the advantages of indigenous Fijians. (shrink)

It is the contention of this paper that some progress in alleviating the social and environmental problems which are beginning to face Papua New Guinea can be achieved by supporting traditional Melanesian values through maintaining the customary system of communal land tenure. In accordance with this aim, I will proceed to contrast certain Western attitudes towards individual freedom, selfinterested behaviour, individual and communal interests and private ownership with attitudes and values expressed in the traditional Melanesian approach. In order to demonstrate (...) the latter, I will briefly touch upon the phenomenon of wantokism and indicate how the Melanesian values associated with this concept find their locus in the system of customary communal ownership. Subsequently, I will describe how the emergence of a cash economy and the attachment to Western gadgetry and products have effected injury to the environment and undermined values which have previously maintained Melanesian social cohesion. While admitting that little can be done to eradicate the desire for cash and the products it can buy, I suggest that Melanesian communities and the environment itself would receive more protection if future development in Papua New Guinea embraced a system which incorporated certain of the traditional Melanesian values through the preservation of the communal form of land tenure. Ultimately, I suggest a way in which customary communal land tenure can be integrated into the established Anglo-Australian legal system. (shrink)

Recently there has been considerable controversy over the environmental impact of Christian teaching. During the beginnings of our increased awareness of the ecological crisis, several strong papers appeared condemning Christianity for encouraging environmental exploitation. Recently a number of works have sought to defend the Judeo-Christian tradition by emphasizing different aspects of a message that allegedly promotes environmentally friendly behavior. Overall, however, these interpretations exhibit doubtful ontic significance. It is the contention of this paper that Christianity evolved profoundly after the Renaissance (...) and the Reformation and with attendant intellectual changes encouraged an exploitative attitude towards the natural environment. These post Renaissance attitudes suppressed or supplanted the attitudes towards the created order engendered by Hellenic thought that were prominent during the Middle Ages. This change in perspective is most evident in the promotion of instrumental reason rather than a model of rationality based on contemplation, which had been the inheritance of Classical philosophy. (shrink)

In this paper I discuss the managerial template that has become the normative model for the organization of the university. In the first part of the paper I explain the corporatization of academic life in terms of the functional relationships that make up the organizational components of the commercial enterprise and their inappropriateness for the life of the academy. Although there is at present a significant body of literature devoted to this issue, the goal of this paper is to explain (...) the genesis of this phenomenon through a reference to the ideology that characterizes our modern secular age. This is the subject of the second part of the paper. Most texts seek to explain this ideological development either through the ever increasing dominance of economic rationalism, perceived conservatism of collegial forms of governance, the necessity to transfer fiscal responsibility in tight budgetary periods, the decline of the Keynesian ‘welfare consensus’, or the legacy of the power regimes that began to take shape in the liberal societies of the 19th century. I trace this development to the beginnings of Modernity and the Cartesian bifurcation that separated the material world from its spiritual and intellectual source and thereby overthrew the hierarchy of related values that informed both nature and human organization. In articulating this argument I make reference to the thought of Jacques Maritain, Charles Taylor and René Guénon. (shrink)

BACKGROUND: Serotonin transporter promoter genotype appears to increase risk for depression in the context of stressful life events. However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood. METHOD: Thirty-nine unselected seven-year-old children completed a negative mood induction procedure and a Self-Referent Encoding Task designed to measure positive and negative schematic processing. Children were also genotyped for the 5-HTTLPR gene. (...) RESULTS: Children who were homozygous for the short allele of the 5-HTTLPR gene showed greater negative schematic processing following a negative mood prime than those with other genotypes. 5-HTTLPR genotype was not significantly associated with positive schematic processing. LIMITATIONS: The sample size for this study was small. We did not analyze more recently reported variants of the 5-HTTLPR long alleles. CONCLUSIONS: 5-HTTLPR genotype is associated with negative information processing styles following a negative mood prime in a non-clinical sample of young children. Such cognitive styles are thought to be activated in response to stressful life events, leading to depressive symptoms; thus, cognitive styles may index the "stress-sensitivity" conferred by this genotype. (shrink)

OBJECTIVES: Early-emerging, temperamental differences in fear-related traits may be a heritable vulnerability factor for anxiety disorders. Previous research indicates that the serotonin transporter promoter region polymorphism is a candidate gene for such traits. METHODS: Associations between 5-HTTLPR genotype and indices of fearful child temperament, derived from maternal report and standardized laboratory observations, were examined in a community sample of 95 preschool-aged children. RESULTS: Children with one or more long alleles of the 5-HTTLPR gene were rated as significantly more nervous during (...) standardized laboratory tasks than children who were homozygous for the short alleles. Children homozygous for the short alleles were also rated as significantly shyer, by maternal report, than those with at least one copy of the long allele of the 5-HTTLPR gene. CONCLUSIONS: This study extends the literature linking the short alleles of the serotonin transporter promoter region polymorphism to fear and anxiety-related traits in early childhood and adulthood, and is one of very few studies to examine the molecular genetics of preschoolers' temperament using multiple measures of traits in a normative sample. (shrink)

Establishing the basic knowledge, methodology, and technology for a framework for the continuous decoding of hand/arm movement intention was the aim of the ERC-funded project “Feel Your Reach”. In this work, we review the studies and methods we performed and implemented in the last 6 years, which build the basis for enabling severely paralyzed people to non-invasively control a robotic arm in real-time from electroencephalogram. In detail, we investigated goal-directed movement detection, decoding of executed and attempted movement trajectories, grasping correlates, (...) error processing, and kinesthetic feedback. Although we have tested some of our approaches already with the target populations, we still need to transfer the “Feel Your Reach” framework to people with cervical spinal cord injury and evaluate the decoders’ performance while participants attempt to perform upper-limb movements. While on the one hand, we made major progress towards this ambitious goal, we also critically discuss current limitations. (shrink)

Graphical AbstractIs a two-fold approach — preliminary studies based on small samples followed by a large-sample study to check reproducibility — in the search for biomarkers really prudent?

This book aims to provide scientists and engineers, and those interested in scientific issues, with a concise account of how the nature of scientific knowledge evolved from antiquity to a seemingly final form in the Twentieth Century that now strongly limits the knowledge that people would like to gain in the Twenty-first Century. Some might think that such issues are only of interest to specialists in epistemology (the theory of knowledge); however, today's major scientific and engineering problems--in biology, medicine, environmental (...) science, etc.--involve enormous complexity, and it is precisely this complexity that runs up against the limits of what is scientifically knowable. To understand the issue, one must appreciate the radical break with antiquity that occurred with the birth of modern science in the Seventeenth Century, the problems of knowledge and truth engendered by modern science, and the evolution of scientific thinking through the Twentieth Century. While originally aimed at practicing scientists and engineers, it is my hope that this book can provide a generally educated person with a basic understanding of how our perspective on scientific knowledge has evolved over the centuries to escape pre-Galilean commonsense thinking. Such an appreciation is not only beneficial for one's general education, but is important for non-scientists who must teach young students or make policy decisions in government or business. (shrink)

To accept ‘pragmatic encroachment’ is to take the view that whether you are in a position to know is in part a function of practical stakes. This position strikes many as not just unorthodox but extremely implausible. According to Jeremy Fantl and Matthew McGrath (F&M), however, the best account of the prima facie oddity of certain utterances incorporates just such a pragmatist maneuver. In reaching this conclusion, F&M begin with Trent Dougherty and Patrick Rysiew’s (D&R’s) theory as the best (...) on offer (2009a: 63/2009b: 20), but go on to raise objections to D&R’s recent account of the relevant oddity in purely pragmatic (i.e., extra-semantic) terms and to develop it in directions quite inimical to the general outlook established in D&R 2009 and D&R forthcoming. In this brief note, we reply to F&M’s objections and show that their development in the direction of interest-relativism is ill-founded: the relevant phenomena provide no grounds for budging on the issue of pragmatic encroachment. In addition, in the course of meeting F&M’s objections, an original account of certain Moore-paradoxical sentences is given, and the issue of how probable a proposition needs to be to be known is addressed. The result is a quite general defense of a commonsense, evidence-based approach to the relevant phenomena (quite apart from a defense of D&R). (shrink)

Dougherty, R., Critical points in an algebra of elementary embeddings, Annals of Pure and Applied Logic 65 211-241.Given two elementary embeddings from the collection of sets of rank less than λ to itself, one can combine them to obtain another such embedding in two ways: by composition, and by applying one to the other. Hence, a single such nontrivial embedding j generates an algebra of embeddings via these two operations, which satisfies certain laws . Laver has shown, among other (...) things, that this algebra is free on one generator with respect to these laws.The set of critical points of members of this algebra is the subject of this paper. This set contains the critical point κ0 of j, as well as all of the other ordinals κn in the critical sequence of j ). But the set includes many other ordinals as well. The main result of this paper is that the number of critical points below κn grows so quickly with n that it dominates any primitive recursive function. In fact, it grows faster than the Ackermann function, and even faster than a slow iterate of the Ackermann function. Further results show that, even just below κ4, one can find so many critical points that the number is only expressible using fast-growing hierarchies of iterated functions. (shrink)

Hausdorff's paradoxical decomposition of a sphere with countably many points removed actually produced a partition of this set into three pieces A,B,C such that A is congruent to B, B is congruent to C, and A is congruent to B ∪ C. While refining the Banach–Tarski paradox, R. Robinson characterized the systems of congruences like this which could be realized by partitions of the sphere with rotations witnessing the congruences: the only nontrivial restriction is that the system should not require (...) any set to be congruent to its complement. Later, J. F. Adams showed that this restriction can be removed if one allows arbitrary isometries of the sphere to witness the congruences. The purpose of this paper is to characterize those systems of congruences which can be satisfied by partitions of the sphere or related spaces into sets with the property of Baire. A paper of Dougherty and Foreman gives a proof that the Banach–Tarski paradox can be achieved using such sets, and gives versions of this result using open sets and related results about partitions of spaces into congruent sets. The same method is used here; it turns out that only one additional restriction on a system of congruences is needed to make it solvable using subsets of the sphere with the property of Baire with free rotations witnessing the congruences. Actually, the result applies to any complete metric space acted on in a sufficiently free way by a free group of homeomorphisms. We also characterize the systems solvable on the sphere using sets with the property of Baire but allowing all isometries. (shrink)

A famous result of Hausdorff states that a sphere with countably many points removed can be partitioned into three pieces A, B, C such that A is congruent to B, B is congruent to C, and A is congruent to B ∪ C; this result was the precursor of the Banach–Tarski paradox. Later, R. Robinson characterized the systems of congruences like this which could be realized by partitions of the sphere with rotations witnessing the congruences. The pieces involved were nonmeasurable. (...) In the present paper, we consider the problem of which systems of congruences can be satisfied using open subsets of the sphere ; of course, these open sets cannot form a partition of the sphere, but they can be required to cover "most of" the sphere in the sense that their union is dense. Various versions of the problem arise, depending on whether one uses all isometries of the sphere or restricts oneself to a free group of rotations, or whether one omits the requirement that the open sets have dense union, and so on. While some cases of these problems are solved by simple geometrical dissections, others involve complicated iterative constructions and/or results from the theory of free groups. Many interesting questions remain open. (shrink)

This paper attempts a reexamination of classical natural law theory and argues that such theory is properly understood as a meta-ethic rather than as a body of norms. As a meta-ethic, it speaks to topics such as ethical reasoning, the movement from descriptive to normative assertions, the use of science in ethics, the extra-legal grounds for judicial decision, judicial activism and the societal basis of law.

The purpose of this study was to investigate the attitudes of decision-makers toward the use of care robots in welfare services. We investigated their knowledge regarding the use of care robots in welfare services as well as their attitudes toward using robots in their own care and in the care of various user groups, for example, children, youths, and older people. We conducted an online survey with a range of Finnish decision-makers as respondents. The respondents were divided into two groups: (...) service actors and research and development actors. The respondents did not regard themselves as having much knowledge about robotics; however, the results showed that the R&D actors had more overall knowledge of the use of robots than the service actors. The R&D actors were found to be more willing to accept a robot as part of their own care as well as part of the care for various user groups. The contribution of this study is a better understanding of the views of the decision-makers who are or will be in charge of the acquisition of technological devices in welfare services. (shrink)

One must be grateful to Anthony O. Simon for collecting and editing these essays by his distinguished father. Any one of them would be worth the purchase of the book. In an essay entitled “The Philosopher's Calling,” Simon declares, “Generally speaking, the human mind is not at its best in philosophy.” That said, as if to refute his dictum, Simon goes on to show his readers what a mind respectful of a tradition that dates to Plato and Aristotle can say (...) about the human condition. Successive chapters, among others, are entitled “The Concept of Work,” “Nature and the Process of Mathematicalion,” “On Order in Analogical Sets,” and “An Essay on Sensation.”. (shrink)